Hypothesis / aims of study
A new paradigm of the diagnosis, treatment and prevention of urinary tract infections (UTI) is emerging in contemporary medicine. This is based on the knowledge that urine is not sterile but inhabited by diverse microorganisms which form a urobiome. Recurrent UTIs are a leading problem in patients with neurogenic low urinary tract dysfunction (NLUTD). This study aims to assess urinary microbiomes in patients with NLUTD employing the techniques of enhanced quantitative urine culture (EQUC) and real-time polymerase chain reaction (PCR).
Study design, materials and methods
Urinary microbiome has been studied in 118 patients with neurogenic bladder resulting from various neurological conditions and 15 healthy controls. Urine samples for tests have been collected from patients having no symptoms of UTI at the time. Urine cultures were performed with the EQUC method followed by the assessment of antimicrobial resistance. Real-time PCR analyses included a panel of 24 bacterial taxa (“Androflor”, DNA-technology, Russia).
Results
Bacterial growth was detected in 72% of urine samples in the neurogenic bladder group and in 80% of controls. A total of 175 isolates were obtained, ranging from one to six per person (1.76±1.22). The number of isolates in patients with recurrent UTIs was lower than that in others (1±0.58 and 2.25±1.29 correspondingly, р=0.001). Real-time polymerase chain reaction detected bacteria in all urine samples.The most abundant bacteria in neurogenic bladder were as follows: Escherichia coli (20%), Enterococcus faecalis (19%), Staphylococcus spp. (15%), Streptococcus spp. (12%), Klebsiella pneumoniae (9%). Urinary microbiome in controls consisted predominantly of Lactobacillus spp. (40%), Staphylococcus spp. (13%), Bifidobacterium spp. (13%), Streptococcus spp. (7%), Сorynebacterium spp. (7%), Gardnerella vaginalis (6%) in females, and of Corynebacterium glucuronolyticum (33%), Staphylococcus epidermidis (16%), Streptococcus mitis (16,5%), Gardnerella vaginalis (17%) and Lactobacillus crispatus (17%) in males . Urinary microbiomes in patients who voided spontaneously were closer to those in the control group containing, however, a higher proportion of Enterobacterales and Enterococcus spp. Patients who needed intermittent self-catheterization had more diverse microbiomes than patients with indwelling catheters manifested by the presence of Lactobacillus spp., Streptococcus spp., Staphylococcus spp. etc. Isolated Enterobacterales demonstrated low susceptibility to fluoroquinolones (35.5-41.6%) and cephalosporins (56.3-66.7%) while manifesting with high susceptibility to carbapenems (100%), aminoglycosides (93.4-95.8%), fosfomycin (85.5%) and nitrofurantoin (79.2%).
Interpretation of results
Urine of patients with neurogenic low urinary tract dysfunction is inhabited by amount of microorganisms wich are not always can be detected by standart urine culture. EQUC and real-time PCR methods are useful for analysis of urobiome. The study established a link between the microbiome composition, type of the bladder management and incidence of recurrent UTIs. The data about antimicrobial resistance should be taken into account in selecting appropriate antibiotics for the empirical treatment of UTIs in patients with neurogenic bladder.
Concluding message
Enterobacterales and Enterococcus spp. dominate urinary microbiomes of patients with neurogenic bladder. Decreased microbiome species diversity is associated with a higher incidence of recurrent UTIs.
Disclosures
Funding No Clinical Trial No Subjects Human Ethics Committee Local Ethics Committee of Ural State Medical University Helsinki Yes Informed Consent Yes